There are currently efforts to construct tissue grafts in vitro to overcome the many problems posed by currently used artificial extra-corporeal and implanted devices. Such tissue engineering techniques include the creation, design, and fabrication of biological prosthetic devices, in combination with synthetic or natural materials, for the augmentation or replacement of body tissues and organs. However, the use of synthetic materials often results in the release of products and by-products in vivo that induce inflammation, lead to the production of inflammatory mediators, and may induce autoimmune disorders. The use of natural materials such as bovine collagen and decellularized extracellular matrix material from xenogeneic and allogeneic sources pose a risk of passing on pathogens to a recipient, including, such pathogens obtained from both human materials (e.g., HIV and HBV) and non-human materials (e.g., prions associated with bovine materials, and the like). In short, the failure mechanism of most tissue-engineered organs is associated directly with the presence of synthetic materials, which trigger various foreign body responses. This is particularly true of tissue engineered vascular grafts that must operate in the most immune sensitive environment in the body.
Vascular disease is typically associated with a severe narrowing of coronary and/or peripheral arteries which compromise organ function by restricting the flow of blood to downstream organs. There are three treatment strategies to repair these diseased arteries. The simplest repair is a catheter-based therapy called angioplasty, where an inflatable balloon is introduced via catheter to the damaged area and then expanded, thus disrupting the atherosclerotic plaque. Although these procedures are relatively inexpensive and pose little threat to the patient, angioplasty is associated with very poor long-term patency rates. A more effective version of this treatment involves the placement of a plastic deformable metallic stent inside the artery. This stent, when expanded, helps to hold the artery open after the balloon is removed. The primary limitation associated with stenting is that the synthetic material (usually nickel based steel, stainless steel, or Nitenol) used for the stent initiates a chronic inflammatory response and triggers a migration of cells toward the lumen of the blood vessel. This process, called intimal hyperplasia, results in a second narrowing of the diseased artery (restenosis). The third treatment option is a surgically placed bypass graft, which re-routes blood flow around the blockage through a new conduit, ideally made from a vein or artery harvested from another site in the subject's own body. In large diameter vessels (≧6 mm inside diameter) these bypass conduits can also be made from synthetic materials such as ePTFE. In most cases, clinical treatment strategies try the relatively non-invasive catheter based angioplasty/stenting before advancing to bypass surgery.
Although bypass procedures are known to have the highest long-term efficacy, the cost and risk associated with such an invasive surgical procedure often dictates that stenting is attempted as the primary treatment method.
In an attempt to increase the efficacy of stenting, new-generation stents have been developed that are coated with drug/protein-impregnated polymers. As the polymer resorbs, the drug, which discourages local cell migration or proliferation (intimal hyperplasia), is eluted into the blood stream. These stents have demonstrated phenomenal success rates in mid-term clinical studies (0-2 years), but, their long-term efficacy after the protein coating is completely resorbed is in question. More recently, advances in cell biology and genetic modifications have given rise to another generation of stent technologies, called cell seeded or living stents. In this configuration, cells are seeded onto the struts of the stent and then implanted. Although few clinical studies have been published on this technology, three limitations exist. First, relatively few cells can be loaded onto the small struts of the stent. Second, when the stent is expanded, the struts slide relative to each other, thus scraping many of the cells from the stent. Third, the cell coating does not offer any sort of membrane to either reduce the inflammatory response to the foreign material or to provide a barrier to prevent cell migration through the stent to the lumen of the vessel.